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Husby S, Choung RS, Crawley C, Lillevang ST, Murray JA. Laboratory Testing for Celiac Disease: Clinical and Methodological Considerations. Clin Chem 2024; 70:1208-1219. [PMID: 39099386 DOI: 10.1093/clinchem/hvae098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2023] [Accepted: 05/30/2024] [Indexed: 08/06/2024]
Abstract
BACKGROUND Celiac disease (CeD) has an estimated prevalence of 1%-3%. The classical clinical presentation is malabsorption, but now patients may present with more subtle symptoms such as constipation, osteoporosis, or iron deficiency anemia. Children may also present with poor growth.CeD has a strong genetic component, and high-risk groups include first-degree relatives with CeD, patients with co-existing autoimmune diseases, and patients with chromosomal aberrations. CONTENT Diagnostic tests for CeD include duodenal histology, serology, and genetic testing. Duodenal histology has traditionally been the gold standard of diagnosis. However, serological tests, especially IgA tissue transglutaminase antibodies (TTG-IgA), are widely used and diagnostic algorithms are based primarily on TTG-IgA as a starting point. Human leukocyte antigen typing may also be incorporated to determine genetic risk for CeD. Guidelines for children endorse biopsy avoidance provided high levels of TTG-IgA, with diagnostic accuracy being comparable to duodenal biopsy. Confirmation may be achieved by identifying IgA endomysial antibodies in a separate blood sample. Subjects with low positive TTG-IgA levels and subjects with IgA deficiency need a biopsy to establish a diagnosis of CeD. The clinical follow-up of CeD usually includes a repeat TTG-IgA examination. In adults, healing may be delayed or incomplete, and a rare consequence of refractory celiac disease is transformation to enteric T-cell lymphoma. SUMMARY Laboratory testing, in particular TTG-IgA, plays a central role in the diagnosis and has an accuracy comparable to histology. Diagnostic algorithms utilizing laboratory testing are critical for the development of novel strategies to improve diagnosis.
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Affiliation(s)
- Steffen Husby
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Rok Seon Choung
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, United States
| | - Cæcilie Crawley
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
- Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark
| | - Søren T Lillevang
- Department of Clinical Immunology, Odense University Hospital, Odense, Denmark
| | - Joseph A Murray
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, United States
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DiJoseph K, Weismiller S, Ssentongo P, Dalessio S, Clarke K. Celiac Disease and the Risk of Micronutrient Deficiencies in Ethnic Minority Populations: A Retrospective Cohort Study. Dig Dis 2024; 42:414-418. [PMID: 38838653 DOI: 10.1159/000539179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Accepted: 04/29/2024] [Indexed: 06/07/2024]
Abstract
INTRODUCTION Celiac disease (CD) is a chronic immune-mediated disorder triggered by gluten ingestion in genetically predisposed individuals. Historically, CD was primarily recognized and described as a disease of the Caucasian population. Data from a national survey in 2015 revealed that 0.79% of the population was formally diagnosed with celiac disease, with the non-Hispanic white population having a prevalence of 4-8 times higher than other underrepresented races. Although there is evidence that CD affects minorities at higher than reported rates, there is little data on its effects on minority populations. Our study aimed to characterize celiac-related complications among underrepresented populations in a large health database. METHODS We performed a cohort study among patients aged ≥18, utilizing the TriNetX US Collaborative Network. Two cohorts of patients (minority and non-Hispanic white) with CD were identified between 2016 and 2021. Cohorts were propensity scores matched on demographics and baseline clinical characteristics. Outcomes were assessed up to 1 year after the index event (CD diagnosis), including vitamin/mineral deficiencies and hospital visits. Data were analyzed using the TriNetX Analytics function. RESULTS Each group was matched with 817 patients. Compared to the non-Hispanic white population, the minority group had a similar incidence of iron, vitamin B, and zinc deficiencies. The minority group had a higher risk of vitamin D deficiency, anemia secondary to iron deficiency, inpatient hospital stays, and emergency department visits. CONCLUSION Our results indicate that minority patients with celiac disease have a higher incidence of vitamin D and iron deficiency.
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Affiliation(s)
- Kara DiJoseph
- Division of Gastroenterology and Hepatology, Department of Medicine, Penn State College of Medicine, Hershey, Pennsylvania, USA
| | - Scott Weismiller
- Department of Medicine, Penn State College of Medicine, Hershey, Pennsylvania, USA
| | - Paddy Ssentongo
- Department of Medicine, Penn State College of Medicine, Hershey, Pennsylvania, USA
| | - Shannon Dalessio
- Division of Gastroenterology and Hepatology, Department of Medicine, Penn State College of Medicine, Hershey, Pennsylvania, USA,
| | - Kofi Clarke
- Division of Gastroenterology and Hepatology, Department of Medicine, Penn State College of Medicine, Hershey, Pennsylvania, USA
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Maimaris S, Schiepatti A, Biagi F. Systematic review with meta-analysis: Cause-specific and all-cause mortality trends across different coeliac disease phenotypes. Aliment Pharmacol Ther 2024; 59:592-605. [PMID: 38204404 DOI: 10.1111/apt.17867] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Revised: 09/07/2023] [Accepted: 12/22/2023] [Indexed: 01/12/2024]
Abstract
BACKGROUND Data on mortality in coeliac disease are contrasting. AIMS To systematically review the literature on all-cause and cause-specific mortality in coeliac disease compared to the general population, and evaluate differences across clinical phenotypes, geographical regions, and over time. METHODS We searched PubMed and Embase from 1 January 1970 to 31 December 2022 for eligible studies reporting on all-cause and cause-specific mortality in coeliac disease compared to the general population or controls. The protocol was registered on Open Science Framework (https://doi.org/10.17605/OSF.IO/852DN). RESULTS We included 25 studies. All-cause mortality (HR 1.16, 95% CI 1.05-1.27, I2 = 89%), mortality due to malignancies (HR 1.21, 95% CI 1.08-1.36, I2 = 65%) and respiratory disease (HR 1.39, 95% CI 1.04-1.86, I2 = 76%) were increased. Mortality due to non-Hodgkin lymphoma (HR 10.14, 95% CI 2.19-46.88, I2 = 96%) was markedly increased. Mortality significantly decreased in recent decades: 1989-2004 (HR 1.61, 95% CI 1.27-2.03, I2 = 91%), 2005-2014 (HR 1.16, 95% CI 0.99-1.36, I2 = 89%), 2015-2022 (HR 1.19, 95% CI 1.05-1.35, I2 = 93%). All-cause mortality was not increased in dermatitis herpetiformis (HR 0.85, 95% CI 0.73-0.99, I2 = 40%) and undiagnosed coeliac disease (HR 1.09, 95% CI 0.95-1.25, I2 = 0%). Mortality was increased in the UK (HR 1.23, 95% CI 1.03-1.47, I2 = 91%) but not Scandinavia (HR 1.01, 95% CI 0.91-1.13, I2 = 81%). Limitations include high heterogeneity and lack of data for many countries. CONCLUSION Mortality in coeliac disease is increased, predominantly due to malignancies-particularly non-Hodgkin lymphoma-although differing significantly across disease phenotypes. Mortality of patients with coeliac disease has significantly decreased in recent decades. These results may influence diagnosis and management.
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Affiliation(s)
- Stiliano Maimaris
- Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
- Gastroenterology Unit of Pavia Institute, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy
| | - Annalisa Schiepatti
- Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
- Gastroenterology Unit of Pavia Institute, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy
| | - Federico Biagi
- Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
- Gastroenterology Unit of Pavia Institute, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy
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Soheilian Khorzoghi M, Rostami-Nejad M, Yadegar A, Dabiri H, Hadadi A, Rodrigo L. Impact of probiotics on gut microbiota composition and clinical symptoms of coeliac disease patients following gluten-free diet. Contemp Clin Trials Commun 2023; 35:101201. [PMID: 37680267 PMCID: PMC10480319 DOI: 10.1016/j.conctc.2023.101201] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2023] [Revised: 08/03/2023] [Accepted: 08/20/2023] [Indexed: 09/09/2023] Open
Abstract
Coeliac disease (CD) is associated with alterations in gut microbiota composition. This study evaluated the effects of probiotics on gut microbiota composition and clinical symptoms of treated CD patients. In this double-blind, placebo-controlled trial study, 31 CD patients that were randomly classified as probiotics (n = 15) and placebo (n = 16) groups received 109 colony-forming units/capsule for 12 weeks. Fecal samples were collected before and after probiotics, or placebo administration and the changes in intestinal microbiota were assessed by quantitative real-time PCR. Probiotic administration improved the patients' clinical symptoms when compared to the placebo group. Fatigue score was significantly reduced by the intake of probiotic supplements (P = 0.02). Except for Staphylococcus spp., the relative abundances of Bacteroidetes, Lactobacillus spp., Bifidobacterium spp., Clostridium cluster I, Enterobacteriaceae, and Firmicutes were higher in probiotics group. Accordingly, a 12-week multi-strain probiotic treatment regimen may modify the composition of intestinal microbiota and improve GI symptoms in CD patients.
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Affiliation(s)
| | - Mohammad Rostami-Nejad
- Celiac Disease and Gluten Related Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hossein Dabiri
- Department of Microbiology, Faculty of Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Azam Hadadi
- Department of Microbiology, Karaj Branch, Islamic Azad University, Karaj, Iran
| | - Luis Rodrigo
- Gastroenterology and Liver Service, Hospital Universitario Central de Asturias, School of Medicine, University of Oviedo, Spain
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Jabeen S, Khan AU, Ahmed W, Ahmad MUD, Jafri SA, Bacha U, Ali A, Muzammil HS, Alsagaby SA, Al Abdulmonem W, Abdelgawad MA, Riaz M, Mahwish, Nasir M, Zafar A, Tufail T, Imran M, Anwar Faridi T, Aslam M, Abid Shah SF, Farooq S, Awan TN, Ur-Rehman H. Disease specific symptoms indices in patients with celiac disease—A hardly recognised entity. Front Nutr 2022; 9:944449. [PMID: 36159486 PMCID: PMC9494589 DOI: 10.3389/fnut.2022.944449] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2022] [Accepted: 07/22/2022] [Indexed: 12/02/2022] Open
Abstract
Background Celiac disease (CD) was considered a rare disease before and was perceivably only limited to children but now affects almost 1–2% of the global population. This abrupt increase in prevalence is due to advancements in diagnostic criteria and medical facilities but still many countries lack the basic data that can assess the severity of this health issue. The present study was conducted with the aim to assess the common but rarely diagnosed condition with the identification of its underlying secondary ailments. Materials and methods Patients visiting public sector hospitals were recruited and tested for clinical symptoms secondary to gluten-containing foods (wheat and barley, etc.), followed by serological testing for immunoglobulin A, tissue transglutaminase A, and anti-endomysial antibodies. Only seropositive candidates were included in the endoscopic and biopsy examination for the features of villous atrophy and intestinal cell damage. The secondary ailments including anemia, growth retardation, and gastrointestinal symptoms were also documented for the tested positive patients. The modified European Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) criterion was followed throughout the study. Results From 647 suspected cases from March 2018 to July 2019, 113 were confirmed with CD while 58% were female children and 42% were male children. The majority of them were from a lower class (75%) and 26% of them had a positive family history of CD. A total of 67% of patients with CD were underweight while wasting was observed in 38%, and 80% were stunted as well. Of the positively tested patients with CD, 49% had moderate anemia with 15% having severe anemia. Approximately 33% had hypoalbuminemia as well. The majority of them had a mild to severe range of gastrointestinal symptoms, such as abdominal pain, diarrhea, flatus, eructation, diarrhea, and steatorrhea. Conclusion The study finding indicates an increased number of patients diagnosed with CD with an excessive sum of secondary ailments, such as anemia, growth failure, growth retardation, malnutrition, and gastrointestinal symptoms.
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Ambusaidi S, Al Busaidi AM, Al Salmani A, Davidson R, Alshekaili J, Kindi MA, Al Kindi R. Prevalence of Coeliac Disease in Omani Adults with Iron Deficiency Anaemia of Unknown Cause: Case-finding study. Sultan Qaboos Univ Med J 2022; 22:262-267. [PMID: 35673297 PMCID: PMC9155029 DOI: 10.18295/squmj.5.2021.101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Revised: 04/08/2021] [Accepted: 04/27/2021] [Indexed: 11/29/2022] Open
Abstract
Objectives This study aimed to estimate the serological prevalence of coeliac disease in patients with iron deficiency anaemia (IDA) of unknown cause at a primary healthcare facility in Oman. Methods This prospective case-finding study was conducted at the primary care clinics in Sultan Qaboos University Hospital, Muscat, Oman from September 2018 to June 2020. Patients aged 18 to 55 years, with a haemoglobin (Hb) level <11.5 g/dL for males and <11.0 g/dL for females and a ferritin level <30 ng/mL for males and <13 ng/mL for females, were included in the study. Blood samples were obtained for initial serological screening using serum immunoglobulin (Ig)A level; those samples with normal levels of IgA, IgA anti-tissue transglutaminase antibody (tTG) and IgA anti-deamidated gliadin peptide (DGP) were determined. Positive IgA-tTG test was confirmed using IgA-endomysial antibodies. Patients with low IgA levels were tested using IgG-tTG and IgG-DGP. Results A total of 104 patients participated in this study. Eight patients (7.7%) were found to have a positive serological screening result for coeliac disease; of these patients, three (37.5%) had a positive IgA-tTG result. Two of those three (66.7%) had a positive IgA-endomysial antibody. The IgA-DGP result was positive in seven (6.7%) of the 104 patients. Out of those seven patients, two also had a positive IgA tTG. Conclusion Coeliac disease is not a rare disorder. There is a need to increase awareness among healthcare professionals about coeliac disease and its non-classical manifestations such as IDA.
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Affiliation(s)
| | | | - Asma Al Salmani
- Department of Family Medicine & Public Health, Sultan Qaboos University Hospital, Muscat, Oman
| | - Robin Davidson
- Department of Family Medicine & Public Health, University of Bristol, Bristol, United Kingdom
| | - Jalila Alshekaili
- Department of Microbiology & Immunology, Sultan Qaboos University Hospital, Muscat, Oman
| | - Mahmood Al Kindi
- Department of Microbiology & Immunology, Sultan Qaboos University Hospital, Muscat, Oman
| | - Rahma Al Kindi
- Department of Family Medicine & Public Health, Sultan Qaboos University Hospital, Muscat, Oman
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de Sousa Franckilin LR, Dos Santos ACPM, Freitas FEDA, Vieira IG, de Freitas Jorge CE, Neri DG, de Abreu MVC, Fonseca JK, Loffi RG, Foureaux G. Gluten: do only celiac patients benefit from its removal from the diet? FOOD REVIEWS INTERNATIONAL 2022. [DOI: 10.1080/87559129.2021.2024566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Affiliation(s)
| | | | | | | | | | | | | | | | - Renato Guimarães Loffi
- Departamento de Ciência, Tecnologia e Inovação, Treini Biotecnologia Ltda, Belo Horizonte, Brazil
| | - Giselle Foureaux
- Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
- Departamento de Nutrição, Angiogold: Medicina Integrativa, Belo Horizonte, Brazil
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Behrendt I, Fasshauer M, Eichner G. Gluten Intake and All-Cause and Cause-Specific Mortality: Prospective Findings from the UK Biobank. J Nutr 2021; 151:591-597. [PMID: 33382415 DOI: 10.1093/jn/nxaa387] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Revised: 10/20/2020] [Accepted: 11/11/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Gluten has been linked to adverse effects on metabolic and vascular health. OBJECTIVES The present study determines the association between dietary gluten intake and all-cause (primary objective), as well as cause-specific, mortality in people without celiac disease. METHODS Gluten intake was estimated in 159,265 participants of the UK Biobank which is a large multicenter, prospective cohort study initiated in 2006. Cox proportional hazard regression models were used and HRs were determined for all-cause and cause-specific mortality. All models were adjusted for confounders and multiple testing. RESULTS Median (IQR) age was 57 (49-62) y with 52.1% of participants being female. Gluten intake was 8.5 (5.1-12.4) g/d with significantly higher consumption in males [10.0 (6.3-14.1) g/d] than in females [7.2 (4.6-10.7) g/d] (P < 0.0001). During a median follow-up of 11.1 (10.6-11.9) y and 1.8 million person-years, 6259 deaths occurred. Gluten intake was not significantly associated with all-cause mortality after adjusting for confounders (HR: 1.00; 95% CI: 1.00, 1.01; P = 0.59). Dietary gluten was not significantly associated with cancer (HR: 1.00; 95% CI: 1.00, 1.01; raw P = 0.24) or noncancer (HR: 1.00; 95% CI: 0.99, 1.01; raw P = 0.56) mortality. However, gluten intake was positively associated with ischemic heart disease mortality (HR: 1.02; 95% CI: 1.01, 1.04; raw P = 0.003, Holm-adjusted P = 0.04). CONCLUSIONS Gluten intake is not significantly associated with all-cause and cancer mortality in adults without celiac disease. The findings support the hypothesis that limiting gluten intake is unlikely to provide significant overall survival benefits on a population level. The positive association between gluten intake and ischemic heart disease mortality requires further study.
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Affiliation(s)
- Inken Behrendt
- Institute of Nutritional Science, Justus-Liebig University of Giessen, Giessen, Germany
| | - Mathias Fasshauer
- Institute of Nutritional Science, Justus-Liebig University of Giessen, Giessen, Germany.,Department of Internal Medicine (Endocrinology, Nephrology, and Rheumatology), University of Leipzig, Leipzig, Germany.,Integrated Research and Treatment Center (IFB) AdiposityDiseases, Leipzig University Medical Center, Leipzig, Germany
| | - Gerrit Eichner
- Mathematical Institute, Justus-Liebig University of Giessen, Giessen, Germany
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Lebwohl B, Rubio-Tapia A. Epidemiology, Presentation, and Diagnosis of Celiac Disease. Gastroenterology 2021; 160:63-75. [PMID: 32950520 DOI: 10.1053/j.gastro.2020.06.098] [Citation(s) in RCA: 196] [Impact Index Per Article: 49.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Revised: 04/22/2020] [Accepted: 06/06/2020] [Indexed: 12/16/2022]
Abstract
The incidence of celiac disease is increasing, partly because of improved recognition of, and testing for, the disease. The rise in incidence is also due to a real increase of this immune-based disorder, independent of disease detection. The reasons for this true rise in recent decades are unknown but may be related to environmental factors that may promote loss of tolerance to dietary gluten. Strategies to reduce the development of celiac disease have not been proven successful in randomized trials, but the quantity of early-life gluten exposure has been a major focus of prevention efforts. The criteria for the diagnosis of celiac disease are changing, but in adults, diagnosis still depends on the presence of duodenal villous atrophy while the patient is on a gluten-containing diet, along with findings from serology analysis. Although guidelines in the United States continue to mandate a biopsy at all ages, some children receive a diagnosis of celiac disease without a biopsy. If proven accurate and scalable, assays that detect gluten-HLA tetramer complexes might be used in diagnosis to be made in the context of a gluten-free diet without intestinal biopsy.
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Affiliation(s)
- Benjamin Lebwohl
- Department of Medicine, Columbia University Irving Medical Center, New York, New York; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.
| | - Alberto Rubio-Tapia
- Department of Gastroenterology, Hepatology, and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, Ohio
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Abstract
GOALS To compare the diagnostic yield and cost-consequences of 2 strategies, screening regardless of symptoms versus case finding (CF), using a point-of-care test (POCT), for the detection of celiac disease (CD) in primary care, to bridge the diagnostic gap of CD in adults. MATERIALS AND METHODS All subjects under 75 years of age who consecutively went to their general practitioners' offices were offered POCT for anti-transglutaminase immunoglobulin A antibodies. The POCT was performed on all subjects who agreed, and then a systematic search for symptoms or conditions associated with higher risk for CD was performed, immediately after the test but before knowing the test results. The 2 resulting groups were: (a) POCT positive and (b) symptomatic subject at CF. Subjects were defined as symptomatic at CF in the presence of 1 or more symptoms. All POCT-positive or symptomatic subjects at CF were referred to the CD Centers for confirmation of CD. Data on resource consumption were gathered from patients' charts. Cost of examinations, and diagnostic and laboratory tests were estimated with regional outpatient tariffs (Sicily), and a price of &OV0556;2.5 was used for each POCT. RESULTS Of a total of 2197 subjects who agreed to participate in the study, 36 (1.6%) and 671 (30.5%) were POCT positive and symptomatic at CF, respectively. The yield from the screening and CF was 5 new celiac patients. The total cost and mean cost for each new CD case were &OV0556;7497.35 and &OV0556;1499.47 for the POCT screening strategy, and &OV0556;9855.14 and &OV0556;1971.03 for the CF strategy, respectively. Assuming consecutive use of both strategies, performing POCT only in symptomatic subjects at CF, the calculated yield would be 4 new diagnoses with a total cost of &OV0556;2345.84 and a mean cost of &OV0556;586.46 for each newly diagnosed patient. Only 1 patient was celiac despite a negative POCT. CONCLUSIONS Testing symptomatic subjects at CF only by POCT seems the most cost-effective strategy to bridge the diagnostic gap of adult CD in primary care.
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Singh P, Arora A, Strand TA, Leffler DA, Catassi C, Green PH, Kelly CP, Ahuja V, Makharia GK. Global Prevalence of Celiac Disease: Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2018; 16:823-836.e2. [PMID: 29551598 DOI: 10.1016/j.cgh.2017.06.037] [Citation(s) in RCA: 919] [Impact Index Per Article: 131.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2017] [Revised: 06/05/2017] [Accepted: 06/21/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Celiac disease is a major public health problem worldwide. Although initially it was reported from countries with predominant Caucasian populations, it now has been reported from other parts of the world. The exact global prevalence of celiac disease is not known. We conducted a systematic review and meta-analysis to estimate the global prevalence of celiac disease. METHODS We searched Medline, PubMed, and EMBASE for the keywords celiac disease, celiac, celiac disease, tissue transglutaminase antibody, anti-endomysium antibody, endomysial antibody, and prevalence for studies published from January 1991 through March 2016. Each article was cross-referenced with the words Asia, Europe, Africa, South America, North America, and Australia. The diagnosis of celiac disease was based on European Society of Pediatric Gastroenterology, Hepatology, and Nutrition guidelines. Of 3843 articles, 96 articles were included in the final analysis. RESULTS The pooled global prevalence of celiac disease was 1.4% (95% confidence interval, 1.1%-1.7%) in 275,818 individuals, based on positive results from tests for anti-tissue transglutaminase and/or anti-endomysial antibodies (called seroprevalence). The pooled global prevalence of biopsy-confirmed celiac disease was 0.7% (95% confidence interval, 0.5%-0.9%) in 138,792 individuals. The prevalence values for celiac disease were 0.4% in South America, 0.5% in Africa and North America, 0.6% in Asia, and 0.8% in Europe and Oceania; the prevalence was higher in female vs male individuals (0.6% vs 0.4%; P < .001). The prevalence of celiac disease was significantly greater in children than adults (0.9% vs 0.5%; P < .001). CONCLUSIONS In a systematic review and meta-analysis, we found celiac disease to be reported worldwide. The prevalence of celiac disease based on serologic test results is 1.4% and based on biopsy results is 0.7%. The prevalence of celiac disease varies with sex, age, and location. There is a need for population-based prevalence studies in many countries.
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Affiliation(s)
- Prashant Singh
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | | | - Tor A Strand
- Innlandet Hospital Trust, Lillehammer, Norway; Centre for International Health, University of Bergen, Bergen, Norway
| | - Daniel A Leffler
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Gastroenterology Research and Development, Takeda Pharmaceuticals Inc, Cambridge, MA
| | - Carlo Catassi
- Department of Pediatrics, Università Politecnica delle Marche, Ancona, Italy
| | - Peter H Green
- Department of Medicine, Columbia University Medical Center, New York, New York; USA Celiac Disease Center, Columbia University Medical Center, New York, New York
| | - Ciaran P Kelly
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Govind K Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.
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Holmes GKT, Muirhead A. Mortality in coeliac disease: a population-based cohort study from a single centre in Southern Derbyshire, UK. BMJ Open Gastroenterol 2018; 5:e000201. [PMID: 29686881 PMCID: PMC5911148 DOI: 10.1136/bmjgast-2018-000201] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Revised: 03/13/2018] [Accepted: 03/29/2018] [Indexed: 12/13/2022] Open
Abstract
Objective With the advent of screening tests, it was hypothesised that milder cases of coeliac disease coming to diagnosis might have reduced risk of mortality. An earlier publication did not support this view. We have re-examined this issue employing a larger number of patients followed for a further 8 years. Design Patients with coeliac disease from Southern Derbyshire, UK, were followed prospectively from 1978 to 2014 and included those diagnosed by biopsy and serology. Causes of death were ascertained. Standardised mortality ratios were calculated for all deaths, cardiovascular disease, malignancy, accidents and suicides, respiratory and digestive disease. Ratios were calculated for individual causes. Analysis centred on the postdiagnosis period that included follow-up time beginning 2 years from the date of coeliac disease diagnosis to avoid ascertainment bias. Patients were stratified according to date of diagnosis to reflect increasing use of serological methods. Results All-cause mortality increase was 57%. Mortality in the serology era declined overall. Mortality from cardiovascular disease, specifically, decreased significantly over time. Death from respiratory disease significantly increased in the postdiagnosis period. The standardised mortality ratio for non-Hodgkin’s lymphoma was 6.32, for pneumonia 2.58, for oesophageal cancer 2.80 and for liver disease 3.10. Survival in those who died after diagnosis increased by three times over the past three decades. Conclusions Serological testing has impacted on the risk of mortality in coeliac disease. There is an opportunity to improve survival by implementing vaccination programmes for pneumonia and more prompt, aggressive treatments for liver disease.
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13
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Abstract
Coeliac disease occurs in about 1% of people in most populations. Diagnosis rates are increasing, and this seems to be due to a true rise in incidence rather than increased awareness and detection. Coeliac disease develops in genetically susceptible individuals who, in response to unknown environmental factors, develop an immune response that is subsequently triggered by the ingestion of gluten. The disease has many clinical manifestations, ranging from severe malabsorption to minimally symptomatic or non-symptomatic presentations. Diagnosis requires the presence of duodenal villous atrophy, and most patients have circulating antibodies against tissue transglutaminase; in children, European guidelines allow a diagnosis without a duodenal biopsy provided that strict symptomatic and serological criteria are met. Although a gluten-free diet is an effective treatment in most individuals, a substantial minority develop persistent or recurrent symptoms. Difficulties adhering to a gluten-free diet have led to the development of non-dietary therapies, several of which are undergoing trials in human beings.
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Affiliation(s)
- Benjamin Lebwohl
- Celiac Disease Center, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA; Department of Epidemiology, Mailman School of Public Health, Columbia University Medical Center, New York, NY, USA
| | - David S Sanders
- Academic Unit of Gastroenterology, Royal Hallamshire Hospital & University of Sheffield, UK
| | - Peter H R Green
- Celiac Disease Center, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA.
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Shamir R, Hernell O, Leshno M. Cost-Effectiveness Analysis of Screening for Celiac Disease in the Adult Population. Med Decis Making 2016; 26:282-93. [PMID: 16751327 DOI: 10.1177/0272989x06289012] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Background . Celiac disease (CD) is common and, when undiagnosed, may result in increased mortality, suggesting that mass screening could be justified. The authors examined the cost-effectiveness (CE) of such an approach, assuming a higher mortality rate in undiagnosed CD and that adhering to a gluten-free diet (GFD) reduces the mortality rate. Methods . The authors developed a state transition Markov model, evaluating the CE of screening an entire population at the age of 18. Screening strategies included no screening v. screening by IgA antiendomysial antibodies (EMA), IgA human antitissue transglutaminase antibodies (TTG), and TTG verified by EMA. All strategies were examined with and without evaluation for IgA deficiency, and they all included an intestinal biopsy. Effects of variables were examined using sensitivity analysis. Effectiveness was assessed by life expectancy for each strategy and the incremental average CE ratio for each. Results . Base-case analysis revealed US$49,491 and US$572,616 per life year gained for screening compared to no screening using EMA or TTG, respectively. The CE of screening with EMA was most influenced by the prevalence of CD and the standardized mortality ratio (SMR) for untreated CD patients. Screening was cost-effective in populations with a relatively high prevalence of CD or when the SMR for untreated CD patients was higher than 1.5. The model was insensitive to changes in the cost of serological markers and diagnostic endoscopy. Conclusion . Assuming an SMR of 1.5 or higher for untreated CD patients, mass screening for CD is cost-effective in populations with a relatively high prevalence of CD over a wide range of ages at screening. From a CE perspective, EMA is the preferred serological marker for mass screening. Screening for CD would be justified only if the uncertainties regarding the validity of our assumptions are substantiated.
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Affiliation(s)
- Raanan Shamir
- Division of Pediatric Gastroenterology and Nutrition, Meyer Children's Hospital, Haifa, and the Bruce Rappaport School of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
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15
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Abstract
BACKGROUND AND AIMS Celiac disease (CD) is increasingly diagnosed through screening of at-risk groups (relatives of individuals and associated autoimmune disorders). The impact of diagnosis and treatment on screen-detected CD patients is poorly studied, particularly in the United States. We therefore compared the quality of life (QOL) between screen-detected and symptom-detected CD patients. METHODS Patients with a known diagnosis of CD were invited to complete 3 validated survey instruments: the CD Quality of Life (CDQOL), the CD Adherence Test for dietary adherence and the general Psychological General Well-Being index. In addition, demographic details, mode of presentation, and compliance with gluten-free diet (GFD) were assessed. RESULTS The overall response rate was high at 69%. Of 226 responses received, 211 were eligible for inclusion; the median age was 47, and the median duration of GFD was 4 years. One third of the sample (71, 34%) was screen detected. Of these, 57 (80%) had a relative diagnosed with CD, whereas 14 (20%) had an associated condition. Despite being screen detected, 49 (69%) reported symptoms before diagnosis. GFD adherence was excellent and did not differ between groups. Overall, there were no significant differences between screen-detected and symptom-detected patients with regard to CDQOL, CD Adherence Test, and Psychological General Well-Being scores. CONCLUSIONS Screen-detected and symptom-detected CD patients do not differ with regard to QOL or disease adherence as measured by validated disease-specific instruments. A high proportion of screen-detected patients reported symptoms before diagnosis, which often improve with GFD.
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Lionetti E, Gatti S, Pulvirenti A, Catassi C. Celiac disease from a global perspective. Best Pract Res Clin Gastroenterol 2015; 29:365-379. [PMID: 26060103 DOI: 10.1016/j.bpg.2015.05.004] [Citation(s) in RCA: 117] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2015] [Revised: 04/28/2015] [Accepted: 05/07/2015] [Indexed: 01/31/2023]
Abstract
Celiac disease (CD) is one of the commonest lifelong disorders in countries populated by individuals of European origin, affecting approximately 1% of the general population. This is a common disease also in North Africa, Middle East and India. The widespread diffusion of CD is not surprising given that its causal factors (HLA predisposing genotypes and consumption of gluten-containing cereals) show a worldwide distribution. Further studies are needed to quantify the incidence of CD in apparently "celiac-free" areas such as Sub-Saharan Africa and Far East. Several reports have shown that CD is increasing in frequency in different geographic areas. Genetic factors do not explain the rising incidence during the last decades; environmental or lifestyle factors may be responsible for these changes over time. The majority of patients with CD are still undiagnosed all over the world, leading to debate about the need of screening program.
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Affiliation(s)
- Elena Lionetti
- Department of Paediatrics, University of Catania, Via S. Sofia 78, 95124 Catania, Italy.
| | - Simona Gatti
- Department of Paediatrics, Marche Polytechnic University, Ancona, Via Corridoni 11, 60123 Ancona, Italy.
| | - Alfredo Pulvirenti
- Department of Clinical and Molecular Biomedicine, University of Catania, Via S. Sofia 78, 95124 Catania, Italy.
| | - Carlo Catassi
- Department of Paediatrics, Marche Polytechnic University, Ancona, Via Corridoni 11, 60123 Ancona, Italy; The Division of Paediatric Gastroenterology and Nutrition, Center for Celiac Research, MassGeneral Hospital for Children, 55 Fruit Street, Boston, MA 02114, USA.
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Ludvigsson JF, Card TR, Kaukinen K, Bai J, Zingone F, Sanders DS, Murray JA. Screening for celiac disease in the general population and in high-risk groups. United European Gastroenterol J 2015; 3:106-120. [PMID: 25922671 PMCID: PMC4406899 DOI: 10.1177/2050640614561668] [Citation(s) in RCA: 106] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2014] [Accepted: 10/27/2014] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Celiac disease (CD) occurs in approximately 1% of the Western population. It is a lifelong disorder that is associated with impaired quality of life (QOL) and an excessive risk of comorbidity and death. OBJECTIVES To review the literature on screening for CD in relation to the current World Health Organization (WHO) criteria for mass screening. METHODS We performed a PubMed search to identify indexed papers on CD screening with a publication date from 1900 until 1 June 2014. When we deemed an abstract relevant, we read the corresponding paper in detail. RESULTS CD fulfills several WHO criteria for mass screening (high prevalence, available treatment and difficult clinical detection), but it has not yet been established that treatment of asymptomatic CD may reduce the excessive risk of severe complications, leading to higher QOL nor that it is cost-effective. CONCLUSIONS Current evidence is not sufficient to support mass screening for CD, but active case-finding may be appropriate, as we recognize that most patients with CD will still be missed by this strategy. Although proof of benefit is still lacking, screening for CD may be appropriate in high-risk groups.
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Affiliation(s)
- Jonas F Ludvigsson
- Department of Paediatrics, Örebro University Hospital, Örebro, Sweden
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Timothy R Card
- Department of Epidemiology and Public Health, University of Nottingham, Nottingham, UK
| | - Katri Kaukinen
- School of Medicine, University of Tampere, Tampere, Finland
- Department of Internal Medicine, Hospital, Tampere University Hospital, Tampere, Finland
- Department of Internal Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland
| | - Julio Bai
- Department of Medicine, C Bonorino Udaondo Gastroenterology Hospital, Universidad del Salvador, Buenos Aires, Argentina
| | - Fabiana Zingone
- Department of Medicine and Surgery, University of Salerno, Salerno, Italy
| | - David S Sanders
- Regional GI and Liver Unit, Royal Hallamshire Hospital, Sheffield, UK
| | - Joseph A Murray
- Department of Medicine, Department of Immunology, Mayo Clinic College of Medicine, Rochester, USA
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Abstract
OBJECTIVES The aim of the study was to evaluate the gluten-free diet (GFD) adherence after 1 year of follow-up in children with screening-detected celiac disease (CD) in a general population. METHODS A total of 18,325 twelve-year-olds were invited to participate in a population-based CD screening (Exploring the Iceberg of Celiacs in Sweden), of whom 13,279 participated. In 240 children, CD was detected through elevated anti-tissue transglutaminase antibodies 2 (TG2-IgA) and verified by a small-intestinal biopsy. This substudy included 210 children with TG2-IgA, evaluated both at the initial biopsy occasion and at 1-year follow-up. GFD adherence was evaluated by a combination of TG2-IgA measurements and self-reported adherence (n = 193). RESULTS After 1 year, 85% (179/210) had normalized TG2-IgA levels (<5 U/mL). Among those who had >50 U/mL at diagnosis, 25% (16/63) still had elevated TG2-IgA, but for the majority their initial values were more than halved. Most reported a high level of GFD adherence ("always" 82% [158/193] and "often" 16% [30/193]), and 75% [145/193] reported always adhering combined with normalized TG2-IgA. Although reporting that they were always adherent, 13 (6.7%) had not yet normalized their TG2-IgA levels completely; however, a majority of these initially had the highest TG2-IgA levels. CONCLUSIONS GFD adherence is high in adolescents with CD detected by screening of the general population of Swedish 12-year-olds. Almost all of them had normalized serology and reported GFD adherence at the 1-year follow-up. A few adolescents who reported GFD adherence, however, had elevated TG2-IgA levels, suggesting more severe disease and/or nonadherence.
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Ludvigsson JF, Bai JC, Biagi F, Card TR, Ciacci C, Ciclitira PJ, Green PHR, Hadjivassiliou M, Holdoway A, van Heel DA, Kaukinen K, Leffler DA, Leonard JN, Lundin KEA, McGough N, Davidson M, Murray JA, Swift GL, Walker MM, Zingone F, Sanders DS. Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology. Gut 2014; 63:1210-28. [PMID: 24917550 PMCID: PMC4112432 DOI: 10.1136/gutjnl-2013-306578] [Citation(s) in RCA: 778] [Impact Index Per Article: 70.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
A multidisciplinary panel of 18 physicians and 3 non-physicians from eight countries (Sweden, UK, Argentina, Australia, Italy, Finland, Norway and the USA) reviewed the literature on diagnosis and management of adult coeliac disease (CD). This paper presents the recommendations of the British Society of Gastroenterology. Areas of controversies were explored through phone meetings and web surveys. Nine working groups examined the following areas of CD diagnosis and management: classification of CD; genetics and immunology; diagnostics; serology and endoscopy; follow-up; gluten-free diet; refractory CD and malignancies; quality of life; novel treatments; patient support; and screening for CD.
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Affiliation(s)
- Jonas F Ludvigsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden Department of Paediatrics, Örebro University Hospital, Örebro, Sweden
| | - Julio C Bai
- Department of Medicine, Dr C. Bonorino Udaondo Gastroenterology Hospital, Del Salvador University, Buenos Aires, Argentina
| | - Federico Biagi
- Coeliac Centre/1st Department of Internal Medicine, University of Pavia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Timothy R Card
- University of Nottingham, Department of Epidemiology and Public Health, Nottingham City Hospital, Nottingham, UK
| | - Carolina Ciacci
- Department of Medicine and Surgery, University of Salerno, Salerno, Italy
| | - Paul J Ciclitira
- Gastroenterology, Division of Nutritional Sciences, King's College London, The Rayne Institute, St Thomas Hospital, London, UK
| | - Peter H R Green
- Coeliac Disease Center at Columbia University, New York, New York, USA
| | | | - Anne Holdoway
- Registered dietitian and representative of the British Dietetic Association, Bath, Somerset, UK
| | - David A van Heel
- Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Katri Kaukinen
- School of Medicine, University of Tampere, Tampere, Finland Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland Department of Medicine, Seinäjoki Central Hospital, Finland
| | - Daniel A Leffler
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Jonathan N Leonard
- Department of Dermatology, Imperial College NHS Healthcare Trust, St Mary's Hospital, London, UK
| | - Knut E A Lundin
- Department of Gastroenterology, Centre for Immune Regulation, Oslo University Hospital Rikshospitalet, Oslo, Norway
| | | | - Mike Davidson
- Patient Representative & Regional Chairman for Coeliac UK, Sheffield, UK
| | - Joseph A Murray
- Division of Gastroenterology and Hepatology, Department of Immunology Mayo Clinic, Rochester, Minnesota, USA
| | - Gillian L Swift
- Department of Gastroenterology, University Hospital Llandough, Wales, UK
| | - Marjorie M Walker
- Anatomical Pathology, University of Newcastle, Faculty of Health and Medicine, School of Medicine & Public Health, Callaghan, Australia
| | - Fabiana Zingone
- Department of Medicine and Surgery, University of Salerno, Salerno, Italy
| | - David S Sanders
- Gastroenterology and Liver Unit, Royal Hallamshire Hospital & University of Sheffield, Sheffield, UK
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Rubio‐Tapia A, Ludvigsson JF, Murray JA. Epidemiology of Celiac Disease. GI EPIDEMIOLOGY 2014:185-195. [DOI: 10.1002/9781118727072.ch17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Abstract
Celiac disease (CD) is an immune-mediated systemic condition triggered by dietary gluten occurring in genetically susceptible individuals. Our understanding of its numerous and varied clinical presentations has evolved over time, which has contributed to the incidence of CD increasing. In most cases, the diagnosis is readily established and patients promptly improve after commencing a gluten-free diet (GFD). However, in some, the diagnosis is not straightforward and presents a challenge to clinicians. Potential dilemmas include those with positive serology but normal histology, negative serology but abnormal duodenal mucosal histology, failure to respond to a GFD or response to a GFD without evidence of CD. In recent years, development of new assays and modifications to existing diagnostic algorithms for CD has also challenged the traditional role of small-bowel histology as critical in CD diagnosis.
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Affiliation(s)
- Michael X Ma
- Department of Gastroenterology and Hepatology, Royal Perth Hospital, Perth, WA 6001, Australia
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22
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Popp A, Jinga M, Jurcut C, Balaban V, Bardas C, Laurila K, Vasilescu F, Ene A, Anca I, Mäki M. Fingertip rapid point-of-care test in adult case-finding in coeliac disease. BMC Gastroenterol 2013; 13:115. [PMID: 23849178 PMCID: PMC3717015 DOI: 10.1186/1471-230x-13-115] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2013] [Accepted: 07/09/2013] [Indexed: 01/22/2023] Open
Abstract
BACKGROUND Coeliac disease (CD), due to its protean clinical manifestation, is still very under diagnosed in adults and delays in diagnosis may take years and even decades. Simple tools to find cases in primary care may help to identify patients for further diagnostic tests. We have evaluated the usefulness of an on site rapid fingertip whole blood point-of-care test (POCT) for such a purpose. METHODS As CD is known to run within families, we tested 148 healthy relatives of 70 Romanian index cases with biopsy-proven CD (87% of all first-degree family members, median age 36 years) for the presence of circulating autoantibodies. In addition to performing the POCT (which measures blood erythrocyte self-TG2-autoantibody complexes) on site, blood was drawn for later evaluations of serum IgA-class endomysial antibodies (EMA). EMA-positive sera were further tested for transglutaminase 2 antibodies (TG2-IgA). All serological parameters were analyzed blindly in a centralized laboratory that had no knowledge of the on site POCT result. Endoscopic small intestinal biopsies was recommended for all POCT- or EMA-test positive subjects. RESULTS In on site testing the POCT was positive in 12/148 first-degree relatives (8%) and all these subjects were also serum EMA-positive. A positive EMA test was found only in one other subject. All remaining 135 healthy first-degree relatives were negative for both POCT and EMA. Four subjects positive for both POCT and EMA were negative for TG2-IgA. Ten out of thirteen of the antibody-positive subjects agreed to undergo endoscopy. The POCT was found to be positive in 8/9 first-degree relatives having coeliac-type mucosal lesions of grade Marsh 2 (n = 3) or Marsh 3 (n = 6). The three POCT-positive subjects not agreeing to undergo endoscopy were also both EMA- and TG2-IgA-positive. CONCLUSION The fingertip whole blood rapid POCT might fulfill the unmet need for a simple and cheap case-finding biomarker for early detection and presumptive diagnosis of CD. Confirmatory studies are warranted in adult case-finding in specialized outpatient clinics and in primary care.
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Affiliation(s)
- Alina Popp
- University of Medicine and Pharmacy “Carol Davila”, Str. Dionisie Lupu nr. 37, sector 1, 020022 Bucharest, Romania
- Institute for Mother and Child Care “Alfred Rusescu”, Bdv. Lacul Tei nr. 120, sector 2, 020395 Bucharest, Romania
- Tampere Center for Child Health Research, University of Tampere and Tampere University Hospital, Finn-Medi 3, Biokatu 10, 33520 Tampere, Finland
| | - Mariana Jinga
- University of Medicine and Pharmacy “Carol Davila”, Str. Dionisie Lupu nr. 37, sector 1, 020022 Bucharest, Romania
- Central University Emergency Military Hospital “Dr. Carol Davila”, Str. Mircea Vulcanescu nr. 88, sector 1, 010825 Bucharest, Romania
| | - Ciprian Jurcut
- Central University Emergency Military Hospital “Dr. Carol Davila”, Str. Mircea Vulcanescu nr. 88, sector 1, 010825 Bucharest, Romania
| | - Vasile Balaban
- Central University Emergency Military Hospital “Dr. Carol Davila”, Str. Mircea Vulcanescu nr. 88, sector 1, 010825 Bucharest, Romania
| | - Catalina Bardas
- Institute for Mother and Child Care “Alfred Rusescu”, Bdv. Lacul Tei nr. 120, sector 2, 020395 Bucharest, Romania
| | - Kaija Laurila
- Tampere Center for Child Health Research, University of Tampere and Tampere University Hospital, Finn-Medi 3, Biokatu 10, 33520 Tampere, Finland
| | - Florina Vasilescu
- Central University Emergency Military Hospital “Dr. Carol Davila”, Str. Mircea Vulcanescu nr. 88, sector 1, 010825 Bucharest, Romania
| | - Adina Ene
- Institute for Mother and Child Care “Alfred Rusescu”, Bdv. Lacul Tei nr. 120, sector 2, 020395 Bucharest, Romania
| | - Ioana Anca
- University of Medicine and Pharmacy “Carol Davila”, Str. Dionisie Lupu nr. 37, sector 1, 020022 Bucharest, Romania
- Institute for Mother and Child Care “Alfred Rusescu”, Bdv. Lacul Tei nr. 120, sector 2, 020395 Bucharest, Romania
| | - Markku Mäki
- Tampere Center for Child Health Research, University of Tampere and Tampere University Hospital, Finn-Medi 3, Biokatu 10, 33520 Tampere, Finland
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Abstract
This review will try to address the question of whether we are diagnosing too many people with coeliac disease. The key reasons for diagnosing coeliac disease may be that it is a common condition affecting up to 1% of the adult population. Delays in diagnosis are common. The average time delay reported by Coeliac UK (National Medical Patient Charity), for patients with symptoms prior to the diagnosis being made is 13 years. For every adult case detected, it is estimated that there are eight cases not detected. Patients with coeliac disease have an associated morbidity and mortality. In addition, quality of life studies suggest that the majority of patients benefit from a gluten-free diet (GFD). Furthermore, the GFD reduces or alleviates the risk of the associated complications. All of these facts could even be used to support the argument for screening! However, conversely the tests for coeliac disease are not 100% sensitive and specific. In addition, we do not know whether patients with milder symptoms will derive less benefit from treatment and are at less risk of complications. Furthermore, evidence presented in this review suggests that actual outcomes for screening studies in an adult population have revealed poor uptake and subsequently difficulties with adherence. What little published data that are available also infers that individuals recognised through screening programmes could have been detected if carefully questioned for symptoms. There is evidence to suggest that diagnosing celiac disease is cost-effective and that the diagnostic costs are offset by reduced medical expenditures, reduced hospital and general practice attendances, but this view depends on the population prevalence of coeliac disease. We believe on the basis of the evidence presented in this review that we are not diagnosing too many adults with coeliac disease. However, the authors consider case-finding with a low threshold for serological testing to be the optimal approach. If you look for coeliac disease you will find it.
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Abstract
This article reviews the risk of mortality and malignancy in celiac disease (CD) and examines the evidence of the protective effect of a gluten-free diet (GFD) on mortality and malignancy. Population-based studies have confirmed that patients with diagnosed CD are at increased risk of mortality. However, patients with CD do not seem to be at an increased risk of malignancy, except for an increased risk of lymphoproliferative malignancy and gastrointestinal cancer. The evidence that a GFD reduces the risk of mortality is weak, but there is some evidence suggesting that a GFD may reduce the risk of lymphoproliferative malignancy.
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Lebwohl B, Rubio-Tapia A, Assiri A, Newland C, Guandalini S. Diagnosis of celiac disease. Gastrointest Endosc Clin N Am 2012; 22:661-77. [PMID: 23083985 PMCID: PMC4005880 DOI: 10.1016/j.giec.2012.07.004] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
This article reviews issues related to identifying the appropriate patient to test for celiac disease, the performance characteristics of serologic testing, the role of gene testing for human leukocyte antigen DQ2 and DQ8 haplotypes, and issues related to the performance of small intestinal biopsy. The article concludes with a review of special diagnostic considerations in pediatric patients.
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Affiliation(s)
- Benjamin Lebwohl
- Department of Medicine, Mailman School of Public Health, Celiac Disease Center, Columbia University, New York, NY 10032, USA.
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Baldassarre ME, Laneve A, Fontana A, Manca F, Salvia G, Barcaglioni P, Cella A, Giannuzzo S, Esposito L, Capursi T, Mastrorilli C, Padovano A, Laforgia N. Usefulness of tissue transglutaminase type 2 antibodies in early pregnancy. Immunopharmacol Immunotoxicol 2012; 34:932-6. [PMID: 22537115 DOI: 10.3109/08923973.2012.680470] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Celiac disease (CD), an autoimmune disease triggered by dietary gluten, is a multi-systemic disorder that primarily results in mucosal damage of the small intestine. Reproductive disorders and pregnancy complications have been associated with CD. Conflicting results have been published concerning CD and the risk of impaired fetal growth with reduced birthweight. The aim of our multicentric, perspective, case-control study was to determine the prevalence of undiagnosed CD in mothers of small for gestational age (SGA) newborns in two regions of Italy. The study included 480 mothers: group A consisted of 284 SGA newborns' mothers and group B consisted of 196 appropriate for gestational age (AGA) newborns' mothers. Tissue transglutaminase type 2 antibodies (TG2) IgA and IgG were measured in blood samples. We diagnosed two new cases of CD in asymptomatic mothers. It may be appropriate to include the TG2 to the panel of prenatal blood test.
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Affiliation(s)
- Maria Elisabetta Baldassarre
- Department of Gynecology, Obstetrics and Neonatology, Section of Neonatology and NICU, University of Bari, Bari, Italy.
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Grainge MJ, West J, Solaymani-Dodaran M, Card TR, Logan RFA. The long-term risk of malignancy following a diagnosis of coeliac disease or dermatitis herpetiformis: a cohort study. Aliment Pharmacol Ther 2012; 35:730-9. [PMID: 22288441 DOI: 10.1111/j.1365-2036.2012.04998.x] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2011] [Revised: 11/06/2011] [Accepted: 01/05/2012] [Indexed: 12/13/2022]
Abstract
BACKGROUND People with coeliac disease are known to be at increased risk of malignancy; however, long-term risks of malignancy beyond 10-15 years are largely unstudied. AIM To estimate how long an increased risk of malignancy among coeliac disease patients persists following diagnosis and treatment, using data from a cohort with an average follow-up of 25 years. METHODS People with coeliac disease diagnosed in the Lothian region of Scotland, United Kingdom, were followed up from January 1970 or the date of coeliac disease diagnosis (whichever was later) until the first occurrence of death, emigration, cancer diagnosis or the end of 2004. Standardised incidence ratios were calculated to compare the cancer incidence rates among this group with those from the population of Scotland. RESULTS Overall, the risk of any malignancy in coeliac disease patients compared with the general population was increased 40% [standardised incidence ratio (SIR) = 1.41; 95% CI 1.09-1.78]. An increased risk for cancer overall persisted for up to 15 years, beyond which no overall increase in malignancy risk was observed, although the risk of non-Hodgkin's lymphoma remained raised beyond 15 years (SIR = 5.15; 95% CI 1.40-13.2). In total, there were 14 non-Hodgkin's lymphomas in the cohort, providing an overall incidence of 1.3 per 1000 person-years. CONCLUSIONS The overall risk of malignancy in coeliac patients declines with time after diagnosis and is not significantly increased after 15 years. Most of the increased risk can be attributed to the development of haematological malignancies, despite their very low absolute rate of occurrence.
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Affiliation(s)
- M J Grainge
- Division of Epidemiology and Public Health, School of Community Health Sciences, University of Nottingham, Nottingham City Hospital, Hucknall Road, Nottingham, UK.
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Rosén A, Emmelin M, Carlsson A, Hammarroth S, Karlsson E, Ivarsson A. Mass screening for celiac disease from the perspective of newly diagnosed adolescents and their parents: a mixed-method study. BMC Public Health 2011; 11:822. [PMID: 22017750 PMCID: PMC3229548 DOI: 10.1186/1471-2458-11-822] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2011] [Accepted: 10/21/2011] [Indexed: 12/16/2022] Open
Abstract
Background Mass screening for celiac disease (CD) as a public health intervention is controversial. Prior to implementation, acceptability to the targeted population should be addressed. We aimed at exploring adolescents' and parents' experiences of having the adolescents' CD detected through mass screening, and their attitudes towards possible future mass screening. Methods All adolescents (n = 145) with screening-detected CD found in a Swedish school-based screening study, and their parents, were invited to this study about one year after diagnosis. In all, 14 focus group discussions were conducted with 31 adolescents and 43 parents. Written narrative was completed by 91 adolescents (63%) and 105 parents (72%), and questionnaires returned by 114 parents (79%). Data were analyzed using qualitative content analysis. In addition, narratives and questionnaire data allowed for quantified measures. Results Adolescents and parents described how they agreed to participate "for the good of others," without considering consequences for themselves. However, since the screening also introduced a potential risk of having the disease, the invitation was regarded as "an offer hard to resist." For the majority, receiving the diagnosis was described as "a bolt of lightning," but for some it provided an explanation for previous health problems, and "suddenly everything made sense." Looking back at the screening, the predominant attitude was "feeling grateful for being made aware," but some adolescents and parents also expressed "ambivalent feelings about personal benefits." Among parents, 92% supported future CD screening. The most common opinion among both adolescents and parents was that future CD mass screening should be "a right for everyone" and should be offered as early as possible. However, some argued that it should be "only for sufferers" with symptoms, whereas others were "questioning the benefits" of CD mass screening. Conclusions Although the incentives to participate in the CD screening were partly non-personal, and diagnosis was met with surprise, adolescents and parents felt grateful that they were made aware. They welcomed future CD screening, but suggested that it should be conducted earlier in life. Thus, CD mass screening seemed acceptable to most of those who were diagnosed and their parents.
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Affiliation(s)
- Anna Rosén
- Department of Public Health and Clinical Medicine, Epidemiology and Global Health, Umeå University, Umeå, Sweden.
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Abstract
To meet the principles of screening as described by Wilson and Jungner a disease must be common, a significant health burden, detectable and treatable. The key lies in the early detection and alteration of the natural history of disease. Coeliac disease affects 1 in 100 people. Despite this patients frequently have delays in diagnosis or may remain undetected. There is an associated morbidity and mortality which can be effectively treated by simple means of a gluten-free diet. For these reasons coeliac disease has been suggested as appropriate for mass screening. However, there are caveats to this: a complex clinical spectrum, a natural history that is imperfectly understood, overestimation of morbidity and mortality, poor adherence to treatment, and costs of service provision may argue against the time being right for mass screening. This review article provides the most contemporary overview and reference base to allow any clinician to understand the benefits or limitations of a screening programme for adult coeliac disease.
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Canavan C, Logan RF, Khaw KT, West J. No difference in mortality in undetected coeliac disease compared with the general population: a UK cohort study. Aliment Pharmacol Ther 2011; 34:1012-9. [PMID: 21848796 DOI: 10.1111/j.1365-2036.2011.04811.x] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Studies of mortality in undetected coeliac disease compared with the general population give contradictory findings, suggesting it is either increased fourfold compared with the general population or not at all. AIM To establish all-cause and cause-specific mortality in undiagnosed coeliac disease, identified by anti-endomysial antibody (EMA) positivity, in the Cambridge GP Health Survey cohort. METHOD This cohort was recruited in 1990 from the general population aged 45-76 years. All deaths were ascertained from the Office for National Statistics. Mortality rates were calculated per 1000 person years and adjusted for age, gender, smoking and socioeconomic group using multivariate Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS There were 117,914 patient years of follow-up (median 16.8 years) from 7527 participants. Eighty-seven had undetected coeliac disease, their all-cause mortality rate was 9.4 per 1000 person years (95% CI 5.4-16.1) compared with 12.7 (95% CI 12.1-13.4) in EMA-negative participants. The adjusted all-cause mortality HR was 0.98 (95% CI 0.57-1.69). Death due to cancer and circulatory diseases was not increased, adjusted HR were 1.27 (95% CI 0.57-2.85) and 1.39 (95% CI 0.66-2.92) respectively. CONCLUSIONS We observed no excess overall mortality in people aged over 45 years with undetected coeliac disease compared with the general population, nor any increase in deaths related to circulatory disease or cancer. Our findings do not support screening the general population aged over 45 years, for coeliac disease for the purpose of improving life expectancy.
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Affiliation(s)
- C Canavan
- Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK.
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Rosén A, Ivarsson A, Nordyke K, Karlsson E, Carlsson A, Danielsson L, Högberg L, Emmelin M. Balancing health benefits and social sacrifices: a qualitative study of how screening-detected celiac disease impacts adolescents' quality of life. BMC Pediatr 2011; 11:32. [PMID: 21569235 PMCID: PMC3120678 DOI: 10.1186/1471-2431-11-32] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2010] [Accepted: 05/10/2011] [Indexed: 12/14/2022] Open
Abstract
Background Celiac disease often goes undiagnosed. Mass screening might be an option to reduce the public health burden of untreated celiac disease. However, mass screening is still controversial since it is uncertain whether the benefits of early detection outweigh the possible negative consequences. Before implementation of screening programs, the experiences of those being identified as cases should be considered. The aim of our study was to explore how screening-detected celiac disease impacts adolescents' quality of life, as perceived by themselves and their parents. Methods All adolescents (n = 145) with screening-detected celiac disease found in a Swedish screening study, and their parents, were invited to share their experiences in a qualitative follow-up study. In total, we have information on 117 (81%) of the adolescents, either from the adolescents themselves (n = 101) and/or from their parent/s (n = 125). Written narratives were submitted by 91 adolescents and 105 parents. In addition, 14 focus group discussions involving 31 adolescents and 43 parents were conducted. Data was transcribed verbatim and analyzed based on a Grounded Theory framework. Results The screening-detected celiac disease diagnosis had varying impact on quality of life that related both to changes in perceived health and to the adolescents' experiences of living with celiac disease in terms of social sacrifices. Changes in perceived health varied from "healthy as anyone else with no positive change" to "something was wrong and then changed to the better", whereas experiences of living with celiac disease ranged from "not a big deal" to "treatment not worth the price". Perceptions about living with celiac disease and related coping strategies were influenced by contextual factors, such as perceived support from significant others and availability of gluten-free products, and were developed without a direct relation to experiencing changes in perceived health. Conclusions Screening-detected celiac disease has varying impact on adolescents' quality of life, where their perceived change in health has to be balanced against the social sacrifices the diagnosis may cause. This needs to be taken into account in any future suggestion of celiac disease mass screening and in the management of these patients.
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Affiliation(s)
- Anna Rosén
- Department of Public Health and Clinical Medicine, Epidemiology and Global Health, Umeå University, Umeå, Sweden.
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Huan J, Meza-Romero R, Mooney JL, Vandenbark AA, Offner H, Burrows GG. Single-chain recombinant HLA-DQ2.5/peptide molecules block α2-gliadin-specific pathogenic CD4+ T-cell proliferation and attenuate production of inflammatory cytokines: a potential therapy for celiac disease. Mucosal Immunol 2011; 4:112-20. [PMID: 20736999 PMCID: PMC3012747 DOI: 10.1038/mi.2010.44] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Celiac disease (CD) is a disorder of the small intestine caused by intolerance to wheat gluten and related proteins in barley and rye. CD4(+) T cells have a central role in CD, recognizing and binding complexes of HLA-DQ2.5 bearing gluten peptides that have survived digestion and that are deamidated by tissue transglutaminase (TG2), propagating a cascade of inflammatory processes that damage and eventually destroy the villous tissue structures of the small intestine. In this study, we present data showing that recombinant DQ2.5-derived molecules bearing covalently tethered α2-gliadin-61-71 peptide have a remarkable ability to block antigen-specific T-cell proliferation and inhibited proinflammatory cytokine secretion in human DQ2.5-restricted α2-gliadin-specific T-cell clones obtained from patients with CD. The results from our in vitro studies suggest that HLA-DQ2.5-derived molecules could significantly inhibit and perhaps reverse the intestinal pathology caused by T-cell-mediated inflammation and the associated production of proinflammatory cytokines.
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Affiliation(s)
- J Huan
- Department of Neurology, Oregon Health and Science University, Portland, Oregon, USA
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Biagi F, Klersy C, Balduzzi D, Corazza GR. Are we not over-estimating the prevalence of coeliac disease in the general population? Ann Med 2010; 42:557-61. [PMID: 20883139 DOI: 10.3109/07853890.2010.523229] [Citation(s) in RCA: 69] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Until the 1980s, coeliac disease was considered to be a rare disease, but in the 1990s it became clear that it was a frequent condition. Recently, it was suggested to affect 1 out of 100 subjects in the Western world. To understand what the true prevalence of coeliac disease is in the general population, we conducted a systematic review of published papers. The overall prevalence of coeliac disease in the general population appears to be around 1/160 (6.2‰), but this figure varies widely according to the diagnostic criteria used in the original papers. Prevalence obtained with tissue transglutaminase antibodies only was markedly higher than that obtained through a histological diagnosis. We conclude that the prevalence of coeliac disease in the general population has been over-estimated. This is mainly due to tissue transglutaminase antibodies being used as the only diagnostic tool.
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Abstract
Although the prevalence rates of celiac disease tend to be very similar in different Western populations, mortality rates for this disease vary widely. In this Review we focus on the papers that have addressed this issue so far. We evaluated mortality rates in different forms of celiac disease, such as symptomatic celiac disease, unrecognized celiac disease, dermatitis herpetiformis and refractory celiac disease. We also evaluated the role of possible protective factors, such as adherence to a gluten-free diet, early diagnosis and severity of clinical presentation. Finally, we noticed that the mortality rate for celiac disease seems to be higher in Southern than in Northern Europe and seems to correlate with 'national' gluten consumption. To explain these differences, we propose a hypothesis that links mortality rates to the amount of gluten consumed not only after but also before the diagnosis of celiac disease.
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Affiliation(s)
- Federico Biagi
- Coeliac Centre/First Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, P. le Golgi, 19, 27100 Pavia, Italy.
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Abstract
Coeliac disease is a chronic inflammatory disorder of the small bowel induced in genetically susceptible people by the irritant gluten and possibly other environmental cofactors. The disorder is characterised by a diverse clinical heterogeneity that ranges from asymptomatic to severely symptomatic, and it manifests with frank malabsorption, an increased morbidity attributable to the frequent association with autoimmune disorders and increased mortality resulting from the emergence of T-cell clonal proliferations that predispose the patient to enteropathy-type T-cell lymphoma. Our understanding of the molecular basis for this disorder has improved and enabled the identification of targets for new therapies, although a strict gluten-free diet remains the mainstay of safe and effective treatment. In this Seminar we critically reassess the clinical and diagnostic aspects of this disease and new perspectives in its pathogenesis and treatment.
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Affiliation(s)
- Antonio Di Sabatino
- First Department of Medicine, Centro per lo Studio e la Cura della Malattia Celiaca, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
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Lohi S, Mäki M, Rissanen H, Knekt P, Reunanen A, Kaukinen K. Prognosis of unrecognized coeliac disease as regards mortality: a population-based cohort study. Ann Med 2009; 41:508-15. [PMID: 19551537 DOI: 10.1080/07853890903036199] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND AND AIM Clinically diagnosed coeliac disease patients carry an increased risk of mortality. As coeliac disease is markedly underdiagnosed, we aimed to quantify the risk of mortality in subjects with unrecognized and thus untreated coeliac disease. METHOD Blood samples from 6,987 Finnish adults were drawn in 1978-80, and sera were tested for immunoglobulin A (IgA)-class tissue transglutaminase antibodies (Eu-tTG) in 2001. Positive sera were further analysed for endomysial (EMA) and tissue transglutaminase antibodies by another test (Celikey tTG). EMA- and Celikey tTG-positive cases were compared to negatives as regards mortality in up to 28 years of surveillance, yielding a total follow-up of 147,646 person years. Dates and causes of death were extracted from the nation-wide database. RESULTS Altogether 74 (1.1%) of the participants were EMA- and 204 (2.9%) Celikey tTG-positive. The age- and sex-adjusted relative risk of overall mortality was not increased in either EMA (0.78, 95% CI 0.52-1.18) or Celikey tTG (1.19, 95% CI 0.99-1.42) -positive subjects. However, antibody-positive cases evinced a tendency to die from lymphoma, stroke, and diseases of the respiratory system. CONCLUSIONS The prognosis of unrecognized coeliac disease was good as regards overall mortality, which does not support screening of asymptomatic coeliac disease cases.
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Affiliation(s)
- Sini Lohi
- Paediatric Research Center, Medical School, University of Tampere, Tampere, Finland
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Abstract
Pathogens are exogenous agents capable of causing disease in susceptible organisms. In celiac sprue, a disease triggered by partially hydrolyzed gluten peptides in the small intestine, the offending immunotoxins cannot replicate, but otherwise have many hallmarks of classical pathogens. First, dietary gluten and its peptide metabolites are ubiquitous components of the modern diet, yet only a small, genetically susceptible fraction of the human population contracts celiac sprue. Second, immunotoxic gluten peptides have certain unusual structural features that allow them to survive the harsh proteolytic conditions of the gastrointestinal tract and thereby interact extensively with the mucosal lining of the small intestine. Third, they invade across epithelial barriers intact to access the underlying gut-associated lymphoid tissue. Fourth, they possess recognition sequences for selective modification by an endogenous enzyme, transglutaminase 2, allowing for in situ activation to a more immunotoxic form via host subversion. Fifth, they precipitate a T cell–mediated immune reaction comprising both innate and adaptive responses that causes chronic inflammation of the small intestine. Sixth, complete elimination of immunotoxic gluten peptides from the celiac diet results in remission, whereas reintroduction of gluten in the diet causes relapse. Therefore, in analogy with antibiotics, orally administered proteases that reduce the host's exposure to the immunotoxin by accelerating gluten peptide destruction have considerable therapeutic potential. Last but not least, notwithstanding the power of in vitro methods to reconstitute the essence of the immune response to gluten in a celiac patient, animal models for the disease, while elusive, are likely to yield fundamentally new systems-level insights.
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Malamut G, Matysiak-Budnik T, Grosdider E, Jais JP, Morales E, Damotte D, Caillat-Zucman S, Brousse N, Cerf-Bensussan N, Jian R, Cellier C. Adult celiac disease with severe or partial villous atrophy: a comparative study. ACTA ACUST UNITED AC 2008; 32:236-42. [PMID: 18359595 DOI: 10.1016/j.gcb.2008.02.011] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
BACKGROUND AND AIMS While severe villous atrophy (SVA) is the most typical histological feature in adult celiac disease (ACD), partial villous atrophy (PVA) is now also frequently found. So far, the impact of the severity of villous atrophy on the clinical presentation of ACD has been scarcely investigated. We aimed to compare the clinical, biological and immune features and outcomes in ACD patients presenting with PVA at diagnosis versus patients with SVA. PATIENTS AND METHODS Medical files of 48 patients with ACD diagnosed between 1992 and 2003 were retrospectively studied. The diagnosis was based on the presence of intestinal villous atrophy, with increases in intraepithelial lymphocytes and circulating celiac specific antibodies. Villous atrophy was classified as severe (subtotal and total) or partial. Symptoms, biological signs of malabsorption, immune markers, bone mineral density at diagnosis and response to gluten-free diet were recorded. RESULTS At diagnosis, ten patients (four M/six F) had PVA and 38 patients (five M/33 F) had SVA, with a median age of 54 and 33 years, respectively (p<0.05). Positivity for specific antibodies, HLA typing and frequency of autoimmune disease at diagnosis were similar in both PVA and SVA patients, as was their response to gluten-free diet. Diarrhea, malabsorption syndrome and osteopenia were independent of the degree of villous atrophy. CONCLUSION PVA was observed in 21% of patients with ACD. Except for their older age at diagnosis, patients with PVA presented with similar clinical, biological and immune characteristics and outcomes as did patients with SVA.
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Affiliation(s)
- G Malamut
- Department of Gastroenterology and Hepatology, hôpital européen Georges-Pompidou, 75015 Paris, France.
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Bethune MT, Borda JT, Ribka E, Liu MX, Phillippi-Falkenstein K, Jandacek RJ, Doxiadis GGM, Gray GM, Khosla C, Sestak K. A non-human primate model for gluten sensitivity. PLoS One 2008; 3:e1614. [PMID: 18286171 PMCID: PMC2229647 DOI: 10.1371/journal.pone.0001614] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2007] [Accepted: 01/23/2008] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND AND AIMS Gluten sensitivity is widespread among humans. For example, in celiac disease patients, an inflammatory response to dietary gluten leads to enteropathy, malabsorption, circulating antibodies against gluten and transglutaminase 2, and clinical symptoms such as diarrhea. There is a growing need in fundamental and translational research for animal models that exhibit aspects of human gluten sensitivity. METHODS Using ELISA-based antibody assays, we screened a population of captive rhesus macaques with chronic diarrhea of non-infectious origin to estimate the incidence of gluten sensitivity. A selected animal with elevated anti-gliadin antibodies and a matched control were extensively studied through alternating periods of gluten-free diet and gluten challenge. Blinded clinical and histological evaluations were conducted to seek evidence for gluten sensitivity. RESULTS When fed with a gluten-containing diet, gluten-sensitive macaques showed signs and symptoms of celiac disease including chronic diarrhea, malabsorptive steatorrhea, intestinal lesions and anti-gliadin antibodies. A gluten-free diet reversed these clinical, histological and serological features, while reintroduction of dietary gluten caused rapid relapse. CONCLUSIONS Gluten-sensitive rhesus macaques may be an attractive resource for investigating both the pathogenesis and the treatment of celiac disease.
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Affiliation(s)
- Michael T. Bethune
- Department of Biochemistry, Stanford University, Stanford, California, United States of America
| | - Juan T. Borda
- Tulane National Primate Research Center, Covington, Louisiana, United States of America
| | - Erin Ribka
- Tulane National Primate Research Center, Covington, Louisiana, United States of America
| | - Michael-Xun Liu
- Tulane National Primate Research Center, Covington, Louisiana, United States of America
| | | | - Ronald J. Jandacek
- Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio, United States of America
| | | | - Gary M. Gray
- Department of Medicine, Stanford University, Stanford, California, United States of America
| | - Chaitan Khosla
- Department of Biochemistry, Stanford University, Stanford, California, United States of America
- Department of Chemistry, Stanford University, Stanford, California, United States of America
- Department of Chemical Engineering, Stanford University, Stanford, California, United States of America
| | - Karol Sestak
- Tulane National Primate Research Center, Covington, Louisiana, United States of America
- Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana, United States of America
- *E-mail:
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Miguel Valera J, Hurtado C, Poniachik J, Abumohor P, Brahm J. Estudio de enfermedad celíaca en pacientes con enfermedad por hígado graso no alcohólico y con hepatopatías autoinmunes. GASTROENTEROLOGIA Y HEPATOLOGIA 2008; 31:8-11. [DOI: 10.1157/13114565] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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Sundar N, Crimmins R, Swift G. Clinical presentation and incidence of complications in patients with coeliac disease diagnosed by relative screening. Postgrad Med J 2007; 83:273-6. [PMID: 17403956 PMCID: PMC2600030 DOI: 10.1136/pgmj.2006.052977] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND There is an increased prevalence of coeliac disease (CD) among relatives of those with the disease. AIMS To compare the clinical features in patients with CD detected via family screening with those in patients diagnosed routinely. METHODS Information on screening was provided to relatives of patients. Those who wished to be screened were tested for endomysial and/or tissue transglutaminase antibodies. Duodenal biopsy was performed in those with positive antibodies. The clinical details of the relative screening group were compared with those of 105 patients diagnosed routinely. RESULTS 183 relatives underwent screening, of whom 32 had positive serology, 24 had histology diagnostic of CD, six had normal biopsies and two declined duodenal biopsy. Patients in the relative screening group were younger with a median age of 33 years (range 17-72 years) compared to the routine group which had a median age of 54 years (range 25-88 years). In the relative screening group, there was a male preponderance (M:F ratio 16:8), anaemia at presentation was significantly less common (13% v 58%; p<0.001) and osteoporosis was less frequent (9% v 22%; p<0.244) compared with the routine group. 65% of the relative screening group had gastrointestinal symptoms or anaemia at diagnosis. CONCLUSIONS Patients detected by family screening are younger with a male preponderance, but fewer had anaemia and osteoporosis.
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Affiliation(s)
- Neela Sundar
- Department of Gastroenterology, Llandough Hospital, Penarth, Cardiff, UK.
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Abstract
Is common, underdiagnosed, and can present with non-specific symptoms
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Affiliation(s)
- Roger Jones
- Department of General Practice and Primary Care, KCL School of Medicine, London SE11 6SP
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Park SD, Markowitz J, Pettei M, Weinstein T, Sison CP, Swiss SR, Levine J. Failure to respond to hepatitis B vaccine in children with celiac disease. J Pediatr Gastroenterol Nutr 2007; 44:431-5. [PMID: 17414139 DOI: 10.1097/mpg.0b013e3180320654] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVES To determine whether children with celiac disease (CD) fail to show a response to hepatitis B virus (HBV) vaccine more frequently than children without CD. PATIENTS AND METHODS This was a prospective study that compared the response to HBV, tetanus, rubella, and Haemophilus influenzae type b (Hib) vaccines between children with CD and age- and sex-matched control subjects. RESULTS The study population included 26 patients with CD and 18 age- and sex-matched controls. All had received the full complement of childhood vaccinations. A significantly higher proportion of subjects in the CD group (14 of 26) failed to respond to HBV vaccine compared with controls (2 of 18; 53.9% vs 11.1%; P < 0.05). Patients with CD were 8.33 times more likely to test negative for hepatitis B surface antigen than control subjects (95% CI, 1.5-46.5). By contrast, all of the subjects in both groups tested positive for rubella antibodies; only 1 subject in the CD group tested negative for tetanus antibody versus none in the control group (3.9% vs 0%; P = 1.0). The percentage of subjects who tested negative for Hib antibodies was similar in the 2 groups (CD, 33.3%; control, 44.4%; P = 0.53). CONCLUSIONS More than 50% of children with CD do not show a response to standard vaccination regimens for HBV. Given the large number of children with CD throughout the world, this observation suggests that there is a large HBV-susceptible population despite widespread vaccination. Current immunization strategies may need to be reassessed to protect this population and achieve the goal of universal protection.
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Affiliation(s)
- Seung-Dae Park
- Division of Pediatric Gastroenterology and Nutrition, North Shore-Long Island Jewish Health System, New Hyde Park, NY, USA.
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Kwon JH, Farrell RJ. Recent advances in the understanding of celiac disease: therapeutic implications for the management of pediatric patients. Paediatr Drugs 2007; 8:375-88. [PMID: 17154644 DOI: 10.2165/00148581-200608060-00005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Celiac disease (CD) is an autoimmune condition occurring in genetically susceptible individuals characterized by inflammatory injury to the mucosa of the small intestine after the ingestion of wheat glutens or related barley and rye products. Originally thought to be highly prevalent only in Northern European populations, growing evidence indicates a much higher prevalence in many other regions, including the US as well as South America, North Africa, and Asia. The growing awareness that pediatric patients may present with quite diverse and protean manifestations and the significant impact of CD on childhood development has prompted efforts to increase CD awareness for the early diagnosis and treatment of this disease. The current diagnostic criteria for CD requires characteristic histologic findings in small bowel biopsies and clinical remission when placed on a gluten-free diet. Serologic testing for CD can provide additional support for the diagnosis of CD or a means to assess efficacy and adherence to a gluten-free diet. The mainstay of treatment remains the institution of a gluten-free diet. However, patients with refractory CD may require treatment with immunosuppressant medications. With the increased identification of specific gluten epitopes and understanding of the pathogenesis of CD, future therapies may rely on genetically altering gluten proteins, immunization techniques, or therapies focused on either the development of specific immune tolerance or regulation of mucosal inflammation.
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Affiliation(s)
- John H Kwon
- Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, Maryland, USA
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Abstract
Celiac disease is characterized by small bowel enteropathy, precipitated in genetically susceptible individuals by the ingestion of "gluten," which is a term used to encompass the storage proteins of wheat, rye, and barley. Although the intestine heals with removal of gluten from the diet, the intolerance is permanent and the damage recurs if gluten is reintroduced. This damage causes a wide variety of consequence including maldigestion and malabsorption, resulting in the characteristic, although not universal, features of malnutrition. This article examines recent advances in the understanding of the spectrum of celiac disease, illustrates the impact of celiac disease on nutrition, and describes approaches to the management of the disease.
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Affiliation(s)
- Susan H Barton
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
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Fraser JS, King AL, Ellis HJ, Moodie SJ, Bjarnason I, Swift J, Ciclitira PJ. An algorithm for family screening for coeliac disease. World J Gastroenterol 2006; 12:7805-9. [PMID: 17203524 PMCID: PMC4087546 DOI: 10.3748/wjg.v12.i48.7805] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the level of undiagnosed coeliac disease (CD) in relatives of patients affected by the condition.
METHODS: We collected blood from 914 relatives of probands. We screened these individuals by ELISA for IgA and IgG tTG antibodies, confirming any positive IgA tTG results with an IgA EMA and looked for evidence of IgA deficiency in those who were IgG tTG positive alone, and performed IgG1 EMA in these individuals. We undertook HLA typing where positive screening was found, and this confirmed a strong prevalence of HLA-DQ2 in the coeliac population. Follow-up small intestinal biopsy was undertaken in cases with positive serological screening, wherever possible.
RESULTS: Use of this serological screening algorithm revealed a prevalence of undiagnosed CD in 5%-6% of first degree relatives of probands.
CONCLUSION: Our data suggests that first degree relatives of individuals with CD should be screened for this condition.
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Affiliation(s)
- Jocelyn-S Fraser
- Division of Nutritional Sciences, King's College London, United Kingdom
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Abstract
Coeliac disease is a common condition that is increasingly being recognised as a result of the development of sensitive and specific serology. The diagnosis of coeliac disease and its subsequent treatment with a gluten-free diet have implications for the patient, not just for symptom control but also for the possible effect on quality of life and risk of complications. Whether the mode of presentation of coeliac disease has an effect on survival or risk of complication is yet unclear. This article reviews the available evidence regarding these issues.
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Affiliation(s)
- C J R Goddard
- St John's Hospital, Howden Road West, Livingston, West Lothian EH54 6PP, UK
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Rostom A, Murray JA, Kagnoff MF. American Gastroenterological Association (AGA) Institute technical review on the diagnosis and management of celiac disease. Gastroenterology 2006; 131:1981-2002. [PMID: 17087937 DOI: 10.1053/j.gastro.2006.10.004] [Citation(s) in RCA: 478] [Impact Index Per Article: 25.2] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Alaa Rostom
- Division of Gastroenterology, Foothills Medical Centre, University of Calgary, Calgary, Alberta, Canada
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Menardo G, Brizzolara R, Bonassi S, Marchetti A, Dante GL, Pistone C, Marenco D, Rabellino V, Buscaglia S, Scarso R, Murialdo M, Venturino E, Marino CE, Descalzi D, Minetti F, Bagnasco M, Pesce G. Population screening for coeliac disease in a low prevalence area in Italy. Scand J Gastroenterol 2006; 41:1414-20. [PMID: 17101572 DOI: 10.1080/00365520600815605] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE A screening program was proposed for the village of Carcare (population 5700), located in a region of Italy with an apparently low prevalence of coeliac disease (CD): only 1 patient diagnosed out of 2557 inhabitants. The study group comprised 1002 individuals (568 F, 434 M, age range 13-90 years) recruited from blood donors, secondary school pupils and people referred to the local outpatient facilities for routine blood chemistry. MATERIAL AND METHODS Total IgA, IgA anti-tissue transglutaminase (tTG) (ELISA, recombinant human antigen) and IgA antiendomysium (EMA) (IFI, umbilical cord substrate) antibodies were measured in the serum of all participants. All patients with IgA deficiency were investigated for IgG tTG antibodies, and in the case of disagreement between tTG and EMA, they were typed for HLA DQ2-DQ8 haplotypes. RESULTS Thirteen subjects were positive and 988 negative for autoantibodies (3/988 had IgA deficiency). One serum sample was positive for tTG antibodies but negative for EMA. Ten out of 13 positive subjects consented to undergo duodenal biopsy, which invariably produced evidence of CD despite the absence of clinical signs/symptoms. A post-diagnostic clinical investigation provided evidence showing mild iron deficiency (4 subjects) and osteoporosis (2 subjects). After counselling, all subjects accepted a gluten-free diet. CONCLUSIONS The prevalence of CD in the study group was 1:100 (1.0%; 95% CI: 0.5-1.8%): this indicates that CD is largely underdiagnosed in Carcare. Our results suggest that the low prevalence of CD observed in some regions is likely to be due to underdiagnosis.
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Affiliation(s)
- Giorgio Menardo
- Medicina Interna II ASL2 Savona, Ospedale S.Paolo, Savona, Italy
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Abstract
BACKGROUND There is a well-documented relationship between epilepsy and celiac disease, including a syndrome characterized by epilepsy, occipital calcifications, and celiac disease. REVIEW SUMMARY We report the case of a 23-year-old woman with an 11-year history of refractory epileptic seizures and newly diagnosed biopsy-proven celiac disease with increased antiendomysium immunoglobulin A antibodies. The patient showed a dramatic improvement after starting a gluten-free diet. CONCLUSION This case emphasizes the need to include celiac disease in the differential diagnosis when investigating the etiology of epilepsy in refractory patients.
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Affiliation(s)
- Pilar Canales
- Department of Neurology, Hospital Regional de Talca, Talca, Chile.
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